BackgroundEndoscopic healing is an established treatment target for ulcerative colitis (UC). We have recently validated the Milan ultrasound criteria (MUC) to assess endoscopic activity in UC; a MUC score > 6.2 is a valid cut‐off to discriminate endoscopic activity (Mayo endoscopic subscore > 1).ObjectiveThe aim of this study was to assess the predictive value of MUC on disease course in a prospective cohort of UC patients.MethodsUC patients regardless of disease activity and current therapy, underwent colonoscopy and bowel ultrasound (US) at baseline in a blinded fashion. Correlations between baseline MUC and Mayo endoscopic subscore were assessed using Spearman's rank correlation. UC‐related negative course (defined as the need for corticosteroids, or treatment escalation, or hospitalization, or need for colectomy: a composite outcome) over a median 20 months follow‐up, was investigated using the Kaplan‐Meier method and Cox regression analysis.Results98 UC patients were followed up for a median time of 1.6 years (IQR 0.9¬2.7). Milan ultrasound criteria and Mayo endoscopic subscore significantly correlated at baseline (ρ = 0.653; p < 0.001). 70 patients (71%) had negative disease course during the follow‐up period. Milan ultrasound criteria > 6.2 at baseline was statistically significantly associated with negative disease course (HR: 3.87, 95% CI: 2.25–6.64, p < 0.001). Kaplan–Meier analyses drawed a statistically significantly lower cumulative probability of treatment escalation, need of corticosteroids, hospitalization and colectomy, among patients who had MUC ≤ 6.2 at baseline as compared to patients with MUC > 6.2 (p < 0.05 for all outcomes).Conclusionwe have demonstrated for the first time the value of bowel US and an US score in predicting disease course in UC. Milan ultrasound criteria, a validated US‐based score, predicts disease course in UC. Milan ultrasound criteria ≤ 6.2 may be the new treatment target to achieve to reduce the risk of worse outcomes.